BY: RASAQ NURUDEEN LAJIDE
LETURE NTENT INTRDUTIN GLYGEN BREAKDWN (Glycogenolysis) GLYGEN SYNTESIS (Glycogenesis) REGULATIN F GLYGEN METABLISM MAINTENANE F BLD GLUSE DIABETES MELLITUS AND INSULIN
INTRDUTIN In many organisms, excess glucose is converted to polymeric forms for storage glycogen In vertebrates, glycogen is found primarily in the liver and skeletal muscle Liver glycogen serves as a reservoir of glucose for other tissues when dietary glucose is not available (between meals or during a fast) In humans, the total amount of energy stored as glycogen is far less than the amount stored as fat (triacylglycerol) Glycogen granules are complex aggregates of glycogen and the enzymes that synthesize and degrade it as well as the machinery for regulating these enzymes
GLYGEN BREAKDWN
GLYGEN SYNTESIS 2 N N P P 2 UDP-glucose Uridine diphosphate glucose (UDP-glucose) is the immediate precursor for glycogen synthesis. As glucose residues are added to glycogen, UDP-glucose is the substrate and UDP is released as a reaction product. Nucleotide diphosphate sugars are precursors also for synthesis of other complex carbohydrates, including oligosaccharide chains of glycoproteins, etc.
GLYGEN SYNTESIS 2 P glucose-1-phosphate UDP-Glucose Pyrophosphorylase + P P PP i P UTP N N 2 2 N N P P 2 UDP-glucose
UDP-glucose is formed from glucose-1-phosphate: glucose-1-phosphate + UTP UDP-glucose + PP i PP i + 2 2 P i verall: glucose-1-phosphate + UTP UDP-glucose + 2 P i Spontaneous hydrolysis of the ~P bond in PP i (P~P) drives the overall reaction. leavage of PP i is the only energy cost for glycogen synthesis (one ~P bond per glucose residue).
Glycogenin initiates glycogen synthesis. Glycogenin is an enzyme that catalyzes attachment of a glucose molecule to one of its own tyrosine residues. Glycogenin is a dimer, and evidence indicates that the 2 copies of the enzyme glucosylate one another. Tyr active site active site Tyr Glycogenin dimer
4 6 5 2 3 2 1 UDP-glucose P P Uridine tyrosine residue of Glycogenin 2 N -linked glucose residue 4 6 5 2 3 2 1 2 N + UDP 2 2 A glycosidic bondis formed between the anomeric 1 of the glucose moiety derived from UDP-glucose and the hydroxyl oxygen of a tyrosine side-chain of Glycogenin. UDP is released as a product. 2 N
3 2 2 N -linked glucose residue 4 UDP-glucose 6 5 2 3 2 1 2 N + UDP 2 2 (1 4) linkage 2 N + UDP Glycogenin then catalyzes glucosylation at 4 of the attached glucose (UDP-glucose again the donor), to yield an -linked disaccharide with a(1-4) glycosidic linkage. This is repeated until a short linear glucose polymer with a(1-4) glycosidic linkages is built up on Glycogenin
Glycogen Synthase catalyzes transfer of the glucose moiety of UDP-glucose to the hydroxyl at 4 of the terminal residue of a glycogen chain to form an (1 4) glycosidic linkage: glycogen (n residues) + UDP-glucose glycogen (n +1 residues) + UDP A branching enzyme transfers a segment from the end of a glycogen chain to the 6 hydroxyl of a glucose residue of glycogen to yield a branch with an a(1-6) linkage.
REGULATIN F GLYGEN METABLISM Both synthesis & breakdown of glycogen are spontaneous. If both pathways were active simultaneously in a cell, there would be a "futile cycle" with cleavage of one ~P bond per cycle (in forming UDP-glucose). To prevent such a futile cycle, Glycogen Synthase and Glycogen Phosphorylase are reciprocally regulated Regulation of glycogen metabolism is achieved through (1)ovalent modification of key enzymes (2)Allosteric mechanisms and (3) Regulations by hormones (glucagon, epinephrine and insulin )